tbuckley/cabot-search huggingface dataset:
Abstract 10279: Three-Dimensional Deep-Tissue Imaging of the Right Ventricle Reveals the Complex Remodeling of the Microvascular Network in Right Heart Failure
Authors: Kenzo Ichimura, Mario Boehm, Adam Andruska, Katharina Schimmel, Fan Zhang, Spencer Bonham, Angela Kabiti, Vitaly O Kheyfets, Sushma Reddy, Gordon Wang, John MacArthur, Y. Joseph Woo, Ross Metzger, Edda F Spiekerkoetter
Journal: Circulation (2022)

Introduction: Right ventricular (RV) failure is the leading cause of death in patients with pulmonary arterial hypertension (PAH). Capillary rarefaction has been proposed as the hallmark of RV failure, yet our understanding of the capillary architecture is limited by 2D image analysis. Three-dimensional (3D) confocal deep tissue imaging offers the unparalleled opportunity to characterize the architectural microvascular changes in relationship to cardiomyocytes in pressure-overloaded RV failure. Methods and Results: 250 μm heart tissue slices from mice with RV failure, 7-weeks after Pulmonary Artery Banding (PAB) were harvested and the microvascular network was assessed for density, segment length, diameter, orientation, as well as microvasculature-cardiomyocyte contact area in regions with and without interstitial fibrosis using confocal 3D imaging. Human heart tissue from end-stage PAH patients was compared to controls with normal RV function. In PAB mice, 3D imaging of the RV free wall revealed tortuous, shorter, thicker and higher-branched microvascular segments as well as development of fibrosis compared to Sham animals (Fig A). When corrected for fibrosis, the microvascular density was preserved even in advanced stages of RV failure. Physical contact between the microvasculature and cardiomyocytes was preserved in areas without fibrosis, yet significantly impaired in areas with interstitial fibrosis (Fig B), accompanied by an overexpression of β-myosin heavy chain suggesting local ischemia (Fig C). 3D imaging of human RV tissue of end-stage PAH patients revealed architectural microvascular remodeling that varied depending on etiologies and length of disease yet showed preserved microvascular density. (Fig. D). Conclusions: 3D deep tissue imaging revealed compensatory changes of the microvascular network to maintain a stable cardiomyocyte coverage in pressure-overloaded RV failure, which was impaired in areas of interstitial fibrosis.
Abstract 10142: Stratification of the Risk of Developing Heart Failure in Patients With Left Bundle Branch Block: Approach Using Artificial Intelligence
Authors: Ryuichiro Yagi, Shinichi Goto, Calum A Macrae, Rahul C Deo
Journal: Circulation (2022)

Introduction: Left Bundle Branch Block (LBBB) is a common ECG abnormality associated with impaired ventricular function. However, large individual variation in heart failure (HF) risk in patients with LBBB has been observed. Hypothesis: Subtle phenotypic changes reflecting cardiac dysfunction are present on ECG and are detectable using artificial intelligence (AI). Methods: All 12-lead ECGs with LBBB recorded from 1/1/2015 to 12/31/2019 were identified in our institution, and analyzed as a matrix of the dimension of 12 (representing twelve leads) x 2500 (representing 250Hz x 10 seconds). A 2-dimensional convolutional neural network was trained to detect ECG features related to HF. The model was then applied to an external cohort of patients with LBBB but without history of known HF. Cumulative incidences of HF admission were compared by stratifying according to tertiles of the model output (low, intermediate and high AI score groups) using Kaplan-Meier curves, log-rank test, and Cox proportional hazard model. Results: The test cohort consisted of 2,664 individuals with LBBB and 490 (18.4%) were admitted for HF during median follow-up of 1,091 days (IQR 209-1,666). While 12.6% in the low score group experienced HF hospitalization, 18.0% in the intermediate score group and 24.5% in the high score group were admitted due to HF (high vs low AI score group: hazard ratio (HR) 2.11 [95%CI 1.68-2.65]; intermediate vs low AI score group: HR 1.44 [95%CI 1.13-1.83]; log rank p &lt;0.0001; Figure ). The association between AI score and HF admission was significant after adjusting for patient characteristics and conventional ECG parameters (high vs low AI score group: adjusted HR 1.94 [95%CI 1.52-2.47], p&lt;0.0001; intermediate vs low AI score group: HR 1.34 [95%CI 1.05-1.72], p=0.02), and in a subpopulation with at least 2-years of follow-up (log rank p=0.002). Conclusions: The AI model exhibited excellent discrimination for HF admission risk in patients with LBBB.
Abstract 10057: Cerebral Palsy Patients Admitted for Acute Myocardial Infarction; Insights From the 2019 National Inpatient Sample
Authors: Kamleshun Ramphul, Renuka Verma, Nomesh Kumar, Yogeshwaree Ramphul, Komal Kumari, Petras Lohana, Shaheen Sombans, Fnu Arti, Stephanie G Mejias
Journal: Circulation (2022)

Introduction: Past studies have suggested that respiratory diseases are the most common cause of death among children with cerebral palsy (CP). At the same time, cardiovascular complications and cancer could be the leading killer among adult in those patients. The outcomes of cerebral palsy patients and risk factors following an episode of Acute Myocardial Infarction (AMI) have not been widely examined. Methods: A retrospective study via the 2019 National Inpatient Sample was conducted. Cases with CP diagnosis were retrieved via their appropriate ICD-10 codes (G80.0x). We also filtered to include patients with a principal diagnosis of AMI. Various categorical variables were compared via Chi-Square tests. Results: In 2019, 295 patients with cerebral palsy were admitted with AMI. CP patients were younger (mean age 63.20 vs. 66.93 years) and more common among Whites (86.0%), covered by Medicare (79.7%), and of ages &gt;60 (66.1%). Compared to non-CP patients, CP patients also recorded more cases with depression (20.3% vs. 9.3%) and drug abuse (8.5% vs. 3.0%). However, they had less cases with smoking (28.8% vs. 49.3), obesity (13.6% vs. 21.0%), hyperlipidemia (59.3% vs. 68.6%), old myocardial infarct (8.5% vs. 16.6%), hypertension (78.0% vs. 82.8%), diabetes (35.6% vs. 41.2%), peripheral vascular disease (6.8% vs. 10.6%), acute kidney injury (10.2 % vs. 20.8%), ventricular tachycardia (6.8% vs. 7.2%), and paroxysmal atrial fibrillation (6.8% vs. 9.9%). Only 38.6% of CP patients underwent PCI. Conclusions: CP patients may present with AMI at a younger age and express a higher depression and drug abuse rate. Physicians and providers linked with their care should be encouraged to reach out to them for signs of depression and provide them with adequate facilities to seek treatment.
Abstract 10991: Incidence of Pacing-Induced Cardiomyopathy in Leadless and Traditional Pacemakers: A Retrospective Analysis of 198 Patients
Authors: Rohan M Prasad, Zulfiqar Qutrio Baloch, Khalid Saeed Al-Asad, Adolfo Martinez Salazar, Esosa Ukponmwan, Abbas Ali, John Ip
Journal: Circulation (2022)

Introduction: Transvenous pacemaker (TVP) with right ventricular (RV) apical pacing over 40% has been associated with a 17-25% risk of Pacing-Induced Cardiomyopathy (PICM), defined as a decrease in ejection fraction (EF) by 10% or more. It’s been postulated that a septally placed Leadless Pacemaker (LP) causes less risk of PICM, but the exact incidence is unknown. Methods: We performed a single-center retrospective analysis of adults who received an LP or TVP between January 1, 2014 and April 1, 2022 and had echocardiograms before and after the pacemaker. This study’s outcomes were the RV pacing percentage, change in EF, the need for cardiac resynchronization therapy (CRT) upgrade, and follow-up duration. A Wilcoxon rank-sum test calculated the change in EF. RV time, defined as the duration from pacemaker to echocardiogram in months multiplied by the RV pacing percentage, served as a surrogate for how long the RV was paced. Results: A total of 614 patients were screened and 198 patients were included in the study, where 72 received LP and 126 received TVP. The median follow-up was 480 days. The average of the reported 161 patients with RV percentage pacing for LP was 63.43% and TVP was 71.30% (p=0.14). The incidence of PICM and CRT upgrade in the LP group was 44% and 9.7% in LP and TVP was 37% and 9.5% in TVP (p=0.3 and p&gt;0.9), respectively. After accounting for age, age, sex, LP vs TVP, atrioventricular nodal ablation, RV pacing percentage, and follow-up duration, univariate analysis showed that RV time was significantly different between pacemakers (LP 1,353.97 ± 1,420.56 months vs TVP 926.47 ± 1,395.17 months, p=0.009), but not with CRT (No CRT 1,211.37 ± 1,447.45 months vs CRT 919.34 ± 1,199.54 months, p=0.5). Conclusions: This analysis demonstrated that the incidence of PICM was high in both groups (LP 44% vs TVP 37%). Despite significantly more RV time in patients with LP, there was no difference in CRT upgrade.
Abstract 10610: The Additive Value of Pacemakers and Icds in the Mri Environment Over 18 Years; A Large, Prospective Observational Study
Authors: Robert W Biederman, Loretta Gevenosky, RONALD WILLIAMS, Rich Lombardi, Moneal Shah, Nasir Hussain, Victor Farah, Mark Doyle
Journal: Circulation (2022)

Introduction: MRI is infrequently performed on pts with conventional PM’s and ICDs. While many studies, including MagnaSafe , have unequivocally supported MRI safety in pts with such devices, the clinical value has rarely been considered. Accordingly, we performed an observational, prospective study to determine the 'Additive Value' beyond safety for pts with conventional PM/ICD undergoing clinical MRI. Hypothesis We propose that MRI in PM/ICD pts is crucial to an existing diagnosis and often, substantially alters diagnosis and subsequent management. Methods An MRI Device exam (GE 1.5T,WI) pioneered by cardiologists (&gt;95% over 15 yrs) was performed. Subsequently, a series of defining questions using Boolean Logic Construct were answered within 1 week of MRI by both MRI technologist and MRI physicians: 1) Did the primary diagnosis change? 2) Did MRI provide additional information to existing diagnosis? 3) Was the pre-MRI (tentative) diagnosis confirmed? 4) Did patient management change? If 'Yes' was answered to any of the above questions, it was considered that MRI was of value to pt diagnosisand/or impending therapy. Results: Avg MRI: 28±16min for 1678 consecutive pts of which 1271 (73%) were neuro/neurosurgery, 145 (8%) were musculoskeletal and 323 (19%) were CV cases. Upon review: of the neuro/neurosurgery MRIs, 1106 (87%) provided additional information. The diagnosis changed in 807 (73%), while medical therapy changed in 774 (70%). In only 135 (11%) did MRI simply confirm original diagnosis. For cardiac pts, MRI changed the original diagnosis in 213 (66%). MRI did not contribute in 97(14%) as it was uninterpretable (ICD artifact), while in 43 pts, the diagnosis did not change. Finally, in 145 musculoskeletal pts, MRI provided additional information in 139 (96%) and in 128 (88%), changed pt care, and in 3 pts (2%), simply confirmed the diagnosis. Importantly, with careful attention to device reprogramming and scanner sequences, no safety or device issues were encountered in any pt. Conclusions A dedicated program of utilizing MRI in PM/ICD pts adds substantial clinical value to diagnosis and subsequent management justifying inherent risk. We believe yet another impediment to the advancement of CMR-PM/ICD strategies can become routine and life-changing.
Abstract 10591: Psychometric Testing of the Left Ventricular Assist Device Self-Care Behaviour Scale
Authors: Naoko P Kato, Semyon Melnikov, Quin E Denfeld, Jesus Casida, Anna Stromberg, Tuvia Ben Gal, Christopher S Lee, Tiny Jaarsma
Journal: Circulation (2022)

Introduction: Adequate self-care behaviour is essential for patients with a left ventricular assist device (LVAD) to prevent complications, prolong life, and optimise quality of life. However, this field has lacked valid and reliable measures to assess self-care behaviour among patients with LVAD. To address this need, we recently developed the 33-item LVAD self-care behaviour scale based on a literature review and 2-round Delphi method. Objectives: To evaluate psychometric properties of the new 33-item LVAD self-care behaviour scale. Methods: A cross-sectional survey using a self-administered questionnaire was performed in Japan, Israel, and the United States. Measurement properties of the LVAD self-care behaviour scale were evaluated in reference to the COSMIN Study Design Checklist. In the present study, construct validity, convergent validity, internal consistency, and test-retest reliability were examined. Test-retest reliability was evaluated in a subsample of data (n = 18) from the first and second surveys. Results: Data on 127 patients with LVAD in Israel, Japan, and the USA were analysed (mean age 51±14.3, 81% male). Approximately half had a HeartMate II (47%), while 20% had a HeartMate 3. The median time patients lived with the LVAD was 9.7 months [IQR 3.9-21.8]. Exploratory factor analysis with promax rotation extracted three factors [Factor 1: Monitoring (8 items), Factor 2: Heart failure self-care (5 items), and Factor 3: LVAD self-care (7 items)], and during the analysis 13 items were excluded from the scale. Internal consistency assessed by Cronbach’s alpha was acceptable for the total scale (α=0.80) and the three subscales: Monitoring (α=0.81), Heart failure self-care (α=0.67), and LVAD self-care (α=0.63). The 20-item version of the LVAD self-care behaviour scale had sufficient convergent validity with the LVAD Patient Home Management Adherence Scale (r=0.47, p&lt;0.001). The intraclass correlation coefficient of the total score was 0.58, suggesting adequate test-retest reliability. Conclusions: The 20-item version of the LVAD self-care behaviour scale showed adequate validity and reliability. The scale is ready for use in clinical practice and research. Additional testing might further optimise the scale.
Abstract 10560: Cost-Effectiveness of AF Screening With 2-Week Patch Monitors: The Mhealth Screening to Prevent Strokes Study
Authors: Matthew R Reynolds, Amy B Stein, Evangelos Hytopoulos, Xiaowu Sun, Steven R Steinhubl, David J Cohen
Journal: Circulation (2022)

Introduction. The mHealth Screening to Prevent Strokes (mSToPS) study reported that, compared with standard care, screening older Americans for AF using 2-week Zio patch monitors increased AF diagnosis and oral anticoagulant prescription within one year. The monitored group was also observed to have fewer strokes and deaths at 3 years. The cost-effectiveness of AF screening in this manner has not been explored. Methods. We conducted a health economic analysis of AF screening with Zio patch monitors using patient-level data from the mSToPS study. Clinical outcomes and costs from the payer perspective were obtained from enrollment through 3 years using Aetna claims data. Individual costs, survival and quality-adjusted survival (QALYs) were projected over a lifetime horizon using regression modeling, US life tables and external literature where needed. Potential imbalances between groups were adjusted for with propensity score bin bootstrapping. Results. Study group participants (mean age 74 years, 41% female, median CHA 2 DS 2 -VASC score 3) wore an average of 1.7 two-week monitors at an average cost of $601/person. Over 3 years, monitored individuals were more likely than unmonitored to have outpatient visits, including to cardiology, but less likely to require emergency department visits or hospitalization (see Table). Pharmacy costs over 3 years were similar between groups. Total adjusted 3-year costs, including monitors, were slightly higher (difference $1,170, 95% CI -1315 to 3657) in the monitoring group. In patient-level projections, the monitoring group had slightly better total and quality-adjusted survival (11.91 vs. 11.82 life years, 9.38 vs. 9.30 QALYs) and slightly higher lifetime costs, resulting in an incremental cost-effectiveness ratio of $16,978/QALY gained. Conclusions. Based on lifetime projections derived from the mSToPS study, we found AF screening using 2-week Zio patch monitors to provide high value from a health economic perspective.
Abstract 10469: Time Averaged Lipoprotein(a) Reduction With Sln360, a Novel Sirna Targeting Lp(a,) in Healthy Adults With Elevated Lp(a)
Authors: Curtis Rambaran, Rosamund J Wilson, Daniel I Swerdlow, Giles V Campion, Alison C Scrimgeour, Steven E Nissen
Journal: Circulation (2022)

Introduction: Lipoprotein(a) [Lp(a)] is an important risk factor for atherothrombotic cardiovascular disease for which there are no approved drugs. SLN360 is a short interfering RNA (siRNA) designed to reduce hepatic production of apolipoprotein(a). Primary safety, tolerability and Lp(a) lowering effects have previously been reported in a phase 1 single ascending dose study. Methods: Adults with Lp(a) plasma concentrations ≥ 150 nmol/L at entry and no clinically overt cardiovascular disease were randomized to receive a subcutaneous dose of SLN360 or placebo. The primary efficacy evaluation was percent reduction in Lp(a). Time-averaged reductions were determined to further inform dosing frequency and better evaluate potential clinical benefits. Results: Thirty-two adults received study drug in 4 cohorts. Large, dose-dependent reductions in Lp(a) were observed. For the top 2 doses (300 mg and 600 mg), median (IQR) maximal reductions of 96% (89%, 98%) and 98% (97%, 98%), with reductions of 71% and 81% persisting to day 150, respectively. The time-averaged effect from administration to 150 days, including the time to reach the Lp(a) nadir, was 82% and 87% for the 300 mg and 600 mg groups, respectively. To reflect the anticipated effects of repeat dosing, additional analyses excluded the time to achieve Lp(a) nadir (the first 30 days). This analysis showed 85% and 92% time-averaged median reductions in the 300 mg and 600 mg doses, respectively. Conclusions: In adults with elevated Lp(a), single doses of SLN360 substantially reduced Lp(a) with observed median maximal percent lowering of &gt;95% for doses of 300mg and above, with effects persisting for 150 days. Median time-averaged reductions during 150 days of follow up exceeded 80% in 300 mg and 600 mg treatment groups. Infrequent SLN360 dosing has the potential to substantially reduce Lp(a) to clinically meaningful levels.
Abstract 10618: Modified Rna Ccnd2 Promotes Myocardial Remuscularizationin Lv Infarct by Regulating Cardiomyocyte Cell Cycle
Authors: Lu Wang, Jiacheng Sun, Yang Zhou, Yuhua Wei, Jianyi J Zhang
Journal: Circulation (2022)

The adult mammalian heart has limited capacity to regenerate, due to postnatal cardiomyocyte cell cycle arrest. This study examined whether the cardiomyocyte cell-cycle reactivation can enhance myocardial remuscularization in hearts with acute myocardial infarction (AMI). Because the G1-to-S phase transition of the cell cycle is critically regulated by cyclin D proteins, and the expression of cyclin D2 (CCND2) could regenerate injured myocardium, we hypothesized that a transient and exclusive overexpression of CCND2 in cardiomyocytes can result in myocytes proliferation and therefore, remuscularize myocardial infarct. The transient and exclusive myocyte overexpression of CCND2 was achieved by Specific ModRNA Translation system (SMRTs) 1 . In vitro assessments were performed in hiPSC-derived cardiomyocytes (hiPSC-CMs) by immunofluorescence staining of cell proliferation markers (Ki67, BrdU, PH3, and Aurora B) to evaluate whether cardiomyocyte-specific modified RNA CCND2 ( CMS modRNA-CCND2) could reactivate cell cycle. Using a mouse model of AMI, normal and infarcted mice were compared 4 weeks after AMI to assess the structural and functional outcomes of myocardial injection 100μg CMS modRNA-CCND2. In vitro , the, CMS modRNA-CCND2 resulted in significantly higher CMs cell cycle activity as evidenced by significantly higher percentage of hiPSC-CMs that expressed Ki67 (8.68 ± 1.64 VS 36.68 ± 2.61 , p&lt;0.01), BrdU (8.44 ± 1.14% VS 17.59 ± 0.84%, p&lt;0.01), PH3 (0.51 ± 0.04% VS 1.68 ± 0.09%, p&lt;0.01), and Aurora B (0.47 ± 0.03% VS 1.59 ± 0.07%, P&lt;0.01), CMS modRNA-Luciferase vs CMS modRNA-CCND2, respectively. In vivo, CMs cell cycle activity was significantly increased in SMRT treated hearts 4 weeks post AMI as evidenced by: Ki67 (0.41 ± 0.04% VS 2.00 ± 0.17%, p&lt;0.01), PH3 (0.039 ± 0.004% VS 0.30 ± 0.006%, p&lt;0.01), AMI VS AMI + SMRT, respectively. LV Infarct size also decreased significantly 4 weeks after AMI in AMI + SMRT group of hearts (50.04 ± 1.42% VS 31.28 ± 1.28%, p&lt;0.01). Thus, CMS modRNA-CCND2 could induce myocardial remuscularization by re-activating CM cell- cycle in hearts with AMI. *, equal contribution first author
Abstract 10966: Autoimmune Limbic Encephalitis Mimicking Inferior Myocardial Infarction on ECG
Authors: Armen Zeitjian, Benjamin Noor, Robin Chand
Journal: Circulation (2022)

Case Presentation: A 64 year-old man was brought to the emergency department (ED) after being found down, awake, but unresponsive by family. In the ED, he denied chest pain and shortness of breath. His past medical history included coronary artery disease status-post coronary artery bypass grafting, heart failure with reduced ejection fraction, and paroxysmal atrial fibrillation. On physical exam, he was hemodynamically stable, oriented to self and place with no other significant neurological findings. The field and ED electrocardiograms (ECGs) (Figure 1) were consistent with an acute inferior ST elevation myocardial infarction (STEMI). The patient underwent emergent coronary angiography via left heart catheterization which showed no acute lesions requiring intervention. Initial pertinent lab work included a peak troponin-I of 0.095 ng/mL and serum sodium of 126 mmol/L. Collateral information revealed that the patient has progressive memory loss and intermittent episodes of hand tremors with non-purposeful eye movements. He also had a witnessed faciobrachial dystonic seizure, which is pathognomonic for Leucine-rich, Glioma Inactivated-1 (LGI-1) autoimmune encephalitis. Serum and CSF analyses were positive for LGI-1 IgG antibodies, confirming the diagnosis. The patient was treated with high-dose steroids, IVIG, and valproic acid with improvement in seizure activity and cognitive status, and discharged on prednisone and levetiracetam. Discussion: Per review of the current literature, central nervous system pathology may induce sympathetic overactivity causing transient myocardial injury, referred to as neurogenic stunned myocardium. This can manifest as left ventricular dysfunction, myocardial injury, and/or ECG changes consistent with myocardial infarction. This case presentation highlights an example of a seizure leading to neurogenic stunned myocardium with an ECG showing an acute inferior STEMI.